Shi Le, Du Dongyue, Peng Yunhua, Liu Jiankang, Long Jiangang
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
Oncogenesis. 2020 Oct 31;9(10):98. doi: 10.1038/s41389-020-00276-w.
Cullin (CUL) proteins have critical roles in development and cancer, however few studies on CUL7 have been reported due to its characteristic molecular structure. CUL7 forms a complex with the ROC1 ring finger protein, and only two F-box proteins Fbxw8 and Fbxw11 have been shown to bind to CUL7. Interestingly, CUL7 can interact with its substrates by forming a novel complex that is independent of these two F-box proteins. The biological implications of CUL-ring ligase 7 (CRL7) suggest that the CRL7 may not only perform a proteolytic function but may also play a non-proteolytic role. Among the existing studied CRL7-based E3 ligases, CUL7 exerts both tumor promotion and suppression in a context-dependent manner. Currently, the mechanism of CUL7 in cancer remains unclear, and no studies have addressed potential therapies targeting CUL7. Consistent with the roles of the various CRL7 adaptors exhibit, targeting CRL7 might be an effective strategy for cancer prevention and treatment. We systematically describe the recent major advances in understanding the role of the CUL7 E3 ligase in cancer and further summarize its potential use in clinical therapy.
Cullin（CUL）蛋白在发育和癌症中发挥着关键作用，然而由于其独特的分子结构，关于CUL7的研究报道较少。CUL7与ROC1环指蛋白形成复合物，并且仅有两种F-box蛋白Fbxw8和Fbxw11被证明可与CUL7结合。有趣的是，CUL7能够通过形成一种独立于这两种F-box蛋白的新型复合物来与底物相互作用。泛素连接酶7（CRL7）的生物学意义表明，CRL7不仅可能执行蛋白水解功能，还可能发挥非蛋白水解作用。在现有的基于CRL7的E3连接酶研究中，CUL7在不同背景下既发挥肿瘤促进作用，也发挥肿瘤抑制作用。目前，CUL7在癌症中的作用机制仍不清楚，且尚无针对CUL7的潜在治疗方法的研究。与各种CRL7衔接蛋白所发挥的作用一致，靶向CRL7可能是癌症预防和治疗的有效策略。我们系统地描述了近期在理解CUL7 E3连接酶在癌症中的作用方面取得的主要进展，并进一步总结了其在临床治疗中的潜在用途。
